Biomedical subjects

P Danilo

Publications and source records attributed to P Danilo.

At least 55 records · Page 3Linked to original sources

PubMed1988

Electrophysiologic, inotropic and antiarrhythmic effects of propafenone, 5-hydroxypropafenone and N-depropylpropafenone.

We compared the electrophysiologic, inotropic and antiarrhythmic properties of propafenone and two metabolites, 5-hydroxy (5-OH) propafenone and N-depropyl (N-DP) propafenone. In 18 canine Purkinje fibers with normal maximum diastolic potentials, all drugs (1 x 10(-8) to 1 x 10(-5) M) reduced action potential amplitude and duration. However, propafenone and 5-OH propafenone reduced Vmax in a use-dependent fashion at a lower concentration than N-DP propafenone. In 16 Purkinje fibers, slow response action potentials were induced by 22 mM K+ and isoproterenol, 1 x 10(-6) M. Vmax was comparably reduced by all compounds at 1 x 10(-5) M, but action potential amplitude was not affected by 5-OH propafenone. In 16 other Purkinje fibers in which automaticity at low levels of membrane potential was induced by BaCl2 (0.25 mM), only 5-OH propafenone was effective in slowing the automatic rate at therapeutic concentrations (3 micrograms/ml). In 15 guinea pig papillary muscles, all three drugs had negative inotropic effects at concentrations greater than or equal to 1 x 10(-6) M. In conscious dogs with sustained ventricular tachycardia 24 hr after infarction, we injected propafenone or a metabolite through an atrial cannula. At similar plasma levels, neither propafenone (n = 6) nor N-DP propafenone (n = 6) suppressed the arrhythmia, whereas 5-OH propafenone eliminated ventricular tachycardia in four of six dogs, and was more effective against monomorphic than polymorphic ventricular tachycardia. Hence, the two major metabolites of propafenone have important electrophysiologic effects, and 5-OH propafenone is more potent than the parent compound as a antiarrhythmic drug in the 24-hr Harris dog.

Action Potentials↗

PubMed1987

Alpha 1-adrenergic receptors in the adult, neonatal, and fetal canine heart.

Using the radioligand, iodo-2-[beta-(4-hydroxyphenyl)ethylaminomethyl]tetralone ([125I]-IBE 2254), alpha 1-adrenergic receptors were identified in membranes isolated from fetal, neonatal, and adult canine ventricular myocardium. Binding of the radioligand to alpha 1-adrenergic sites in adult canine heart was rapid, reversible, stereoselective and saturable. Computer analysis of binding data indicated 2 classes of receptors; one with very high affinity and limited capacity (Kd = 13 +/- 9 pM, Bmax = 25 +/- 15 fmol/mg, n = 5) and a second site with lower affinity and greater capacity (Kd = 1.20 +/- 0.43 nM, Bmax = 510 +/- 165 fmol/mg). Two sites were also identified in membranes isolated from fetal and neonatal canine ventricular myocardium. At the higher affinity site, all the age groups displayed similar capacities and affinities. At the lower affinity site, however both fetal and neonatal membranes displayed greater capacity than that of the adult.

Adrenergic alpha-Antagonists↗

PubMed1986

Developmental changes in the effects of beta-adrenergic blocking concentrations of propranolol on canine Purkinje fibers.

We used standard microelectrode techniques to investigate the developmental changes in the effects of the beta-blocker propranolol on canine Purkinje fibers. The effects of propranolol on the transmembrane action potential were similar in neonatal and adult Purkinje fibers. In automatic Purkinje fibers we obtained concentration-response (increase in rate) curves for isoproterenol alone and with an increasing concentration of propranolol. The curve for isoproterenol in neonatal Purkinje fibers had an EC50 of 1.0 X 10(-9) M, about 5-fold lower than in adult Purkinje fibers (EC50 = 5.03 X 10(-9) M, p less than 0.05). At both ages, propranolol caused a parallel, concentration-dependent shift of the response curves for isoproterenol, with no change in the maximum effect. Equiactive dose ratios in presence and absence of 3 concentrations of propranolol were compared by the Schild plot. The pA2 values for adult and neonate Purkinje fibers were 8.32 (8.14-8.46; 95% confidence level) and 8.86 (8.69-9.03; 95% confidence level), respectively. Our results indicate significant (p less than 0.05) developmental changes in the beta-blocking effects of propranolol in canine Purkinje fibers.

Action Potentials↗

PubMed1986

Characteristics of initiation and termination of catecholamine-induced triggered activity in atrial fibers of the coronary sinus.

We studied epinephrine-induced delayed afterdepolarizations and triggered activity in atrial fibers from the canine coronary sinus to determine whether their responses to cardiac pacing would aid in formulating a uniform set of guidelines for differentiating this triggered activity from other arrhythmogenic mechanisms. We used standard microelectrode techniques and compared the delayed afterdepolarizations and triggered activity with those occurring in ouabain-superfused Purkinje fibers. Like Purkinje fibers, the frequency of triggering in the coronary sinus and the coupling interval of the first triggered beat were related directly to the basic drive cycle length, and the delayed afterdepolarization amplitude and frequency of triggering were related to the coupling interval of premature stimuli (S2). However, unlike Purkinje fibers, the coupling interval of the delayed afterdepolarization and of the first triggered beat were independent of the S2. Once initiated, triggered activity in the coronary sinus followed one of four rhythm patterns: in all four, the minimum and equilibrium cycle lengths were independent of the initiating cycle length. Triggered activity was terminated by overdrive and S2 pacing, especially by long episodes of overdrive at short cycle length. The first escape beat after overdrive was linearly related to the overdrive cycle length, resulting in overdrive acceleration. The return cycle length after S2 was linearly related to the S2 coupling interval. Because delayed afterdepolarizations and triggered activity in the coronary sinus respond differently to pacing from those in ouabain-superfused Purkinje fibers, triggered activity in general may not be identified by a uniform set of guidelines.

Action Potentials↗

PubMed1986

Developmental changes in the interactions of cholinergic and beta-adrenergic agonists on electrophysiologic properties of canine cardiac Purkinje fibers.

The parasympathetic nervous system attenuates the effects of sympathetic interventions on the hearts of mature animals. Whereas the vagal mediator, acetylcholine (ACh), alone has minor effects on electrophysiologic properties of the ventricular conducting system, in the presence of sympathetic amines, it induces an accentuated antagonism. Because there are developmental changes in both sympathetic and parasympathetic effects on the heart we studied the parasympathetic and sympathetic interaction in isolated neonatal canine Purkinje fibers (PF), and compared the results to those in adult PF. PF were exposed to isoproterenol (Iso) alone (1 X 10(-9), 1 X 10(-7) and 1 X 10(-5) M) to ACh alone (1 X 10(-7) or 1 X 10(-5) M) and to Iso in the presence of ACh. In adult PF, superfusion with Iso, 10(-5) M, alone shortened action potential duration to 50% repolarization from a control value of 215 +/- 9 to 200 +/- 9 ms (p less than 0.01). Simultaneous superfusion of adult PF with Iso 10(-5) and Ach 10(-5) M decreased the extent of action potential shortening produced by Iso, so that action potential duration to 50% repolarization shortened from a control value of 221 +/- 8 to only 214 +/- 12 ms (p less than 0.01). The response to superfusion with Iso and Ach (10(-5) M) differed significantly from that with Iso alone (p less than 0.01). In contrast, exposure of neonatal PF to Iso (10(-5) M) prolonged action potential duration to 50% repolarization from a control value of 157 +/- 7 to 180 +/- 5 ms (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗

PubMed1986

The inotropic effects of amrinone and milrinone on neonatal and young canine cardiac muscle.

Standard techniques were used to study developmental changes in the effects of amrinone and milrinone on contractile properties of isolated canine cardiac papillary and trabecular muscle. In contrast to milrinone, which induced a positive inotropic effect, amrinone had a negative inotropic effect on the neonatal canine muscles studied. For both drugs there was an age-dependent increase in contractility beyond the neonatal period. The negative inotropic effect of amrinone was not related to a change in phosphodiesterase inhibition, although developmental changes in phosphodiesterase inhibition did occur. These results highlight the differences in the mechanism of action of two similar molecules. They also suggest that use of amrinone as an inotropic agent in the early neonatal period should be viewed with caution.

Age Factors↗

PubMed1985

An evaluation of automaticity and triggered activity in the canine heart one to four days after myocardial infarction.

Both abnormal automaticity and triggered activity induced by delayed afterdepolarizations have been proposed as the primary mechanism for ventricular tachycardia (VT) occurring in dogs 24 hr after ligation of the left anterior descending coronary artery. Because of this controversy, we studied the effects of ventricular pacing and therapeutic concentrations of lidocaine and ethmozin on sustained rhythmic activity of isolated subendocardial preparations excised from the infarct, and on VT in conscious dogs. There were differences in the sustained rhythmic activity cycle length of isolated preparations and the VT cycle length that were attributable to the absence of sympathetic input in the former and its presence in the latter. In isolated tissues, pacing for 1 or 10 beats reset the sustained rhythmic activity and pacing for 1 min induced overdrive suppression. Lidocaine (5 micrograms/ml) had no effect on sustained rhythmic activity but ethmozin (2 micrograms/ml) suppressed it. Delayed afterdepolarizations occurred but appeared to be induced by pacing or by the hyperpolarization associated with recovery. Although delayed afterdepolarizations were infrequent at 24 hr, their frequency increased with the hyperpolarization of the membrane that occurred at 48 to 96 hr after infarction. Delayed afterdepolarizations also occurred more readily when superfusate temperature was lowered. In conscious dogs, pacing the VT for 1 or 10 beats or 1 min had no effect. Lidocaine (2 to 10 micrograms/ml) did not affect the VT but ethmozin (2 to 5 micrograms/ml) increased VT cycle length significantly. Pacing for 1 min in the presence of ethmozin, but not lidocaine, converted VT to sinus rhythm. Our results suggest that although delayed afterdepolarizations occur at 24 hr after infarction in the standard Harris preparation, they are most readily seen as an accompaniment of hyperpolarization, pacing, or lowering of bath temperature. The predominant rhythm at 24 hr appears to be automatic.

Animals↗

PubMed1984

Fetal canine cardiac Purkinje fibers: electrophysiology and ultrastructure.

We studied the ontogenesis of the transmembrane action potential and the ultrastructure of fetal canine Purkinje fibers. Fetal hearts were obtained from fetuses just after implantation to end gestation. Using standard microelectrode recording techniques, we found that action potential characteristics varied linearly over this period of development. Maximum diastolic potential (MDP) ranged from -65 to -85 mV; action potential amplitude (AMP) varied from 100 to 120 mV; maximum upstroke velocity (Vmax) increased from 200 to 550 V/s. Action potential duration measured to 50% repolarization (APD50) increased from 15 to 156 ms while duration measured at full repolarization (APD100) similarly increased from 75 to 236 ms. The relationship between external potassium concentration and membrane potential was equivalent across all stages of fetal development. Tetrodotoxin (TTX, 7.7 X 10(-7) to 1.6 X 10(-5) M) caused concentration-dependent decreases in AMP, Vmax, and APD50. Verapamil (1 X 10(-7) to 1 X 10(-5) M) decreased Vmax and APD50 in a concentration-dependent manner. The effects of both TTX and verapamil were statistically equivalent across all stages of fetal development. Ultrastructural studies of fetal Purkinje fibers showed that myocytes at the earliest stages of development (Purkinje fibers were not visually distinct at this time) were arranged as a tightly packed mosaic with a rounded shape, with a large amount of glycogen, small sparse mitochondria, and relatively large nuclei. Mitotic cells were observed frequently. Purkinje fibers when first identified grossly had fewer myofilaments than working myocardial cells and sarcomeres without M lines. By late gestation, intercalated disks appeared with an increase in surface areas; desmosomes occurred more frequently. Myofilaments are organized around Z bands into rudimentary sarcomeres that still lack M lines. These data indicate that, although the fetal canine Purkinje fiber undergoes marked developmental changes in ultrastructure, cellular electrophysiological changes are more subtle. The action potential has a qualitative appearance similar to those of the neonatal or adult fiber. At no time during fetal development could we find slow-response action potentials.

Action Potentials↗

PubMed1984

Developmental changes in alpha adrenergic effects on canine Purkinje fiber automaticity.

Canine cardiac Purkinje fiber automaticity is modified by adrenergic agonists. Alpha adrenergic agonists slow and beta agonists increase the rate of automatic discharge. These effects vary with maturation and development. We used standard microelectrode techniques to study the effects of the alpha agonist, phenylephrine, on automaticity in isolated neonatal (less than 10 days) and adult canine cardiac Purkinje fibers. Fibers were superfused with 5 X 10(-8) M phenylephrine dissolved in Tyrode's solution. 75% (24/32) of adult and 52% (12/23) of neonatal fibers showed a decrease in rate. The magnitude of the decrease was similar at both ages and the effect was blocked during superfusion with 1 X 10(-9) M phentolamine. The remaining adult and neonatal fibers demonstrated a significant increase in rate in response to 5 X 10(-8) M phenylephrine. This effect was blocked by 5 X 10(-7) M propranolol in the adult group but not in the neonates. However, the increase in rate of fibers from 0- to 2-day neonates was blocked by phentolamine. As an indicator of adrenergic innervation of neonatal hearts, we assayed the myocardial norepinephrine concentration. There was a 6- to 8-fold increase in concentration during the first 10 days of neonatal life, suggesting that innervation was rapidly increasing during this time. In summary, neonatal Purkinje fibers can show an alpha adrenergic-induced acceleration of automatic rate. This alpha adrenergic acceleration is not seen in adults. The change in response from neonate to adult may be effected by growth and development of autonomic nerves and associated changes in receptor function.

Action Potentials↗

PubMed1984

Preparation and electrophysiological characterization of cardiac cell cultures derived from the fetal canine ventricle.

We have developed a primary cardiac cell culture preparation using the fetal canine ventricle. These cultures exhibited widespread and synchronous spontaneous contractile activity, were sensitive to isoproterenol and had the following transmembrane action potential characteristics (means +/- SE): maximum diastolic potential (MDP) -70.9 +/- 0.9 mV; maximum velocity of phase 0 (Vmax) 84 +/- 4 V/s (and tetrodotoxin sensitive); amplitude (AMP) 98.9 +/- 1.1 mV; duration at half amplitude (APD50) 244 +/- 10 ms at a spontaneous cycle length of 1,600 +/- 100 ms. APD50 was linearly dependent on spontaneous cycle length (CL) (slope = 67 ms/s). The action potential of the intact fetal canine ventricle of comparable gestational age had MDP = -67.0 +/- 1.1 mV, Vmax = 127 +/- 6 V/s, AMP = 92.2 +/- 1.6 mV and APD50 = 153 +/- 2 ms at a paced CL of 500 ms. We conclude that myocardial cultures derived from the fetal dog ventricle exhibit electrophysiological characteristics similar to those of the intact canine ventricle, thereby making them a possible alternative to avian and rodent cardiac cultures.

Action Potentials↗

PubMed1984

Effect of alpha adrenergic agonists and blockers on Purkinje fiber transmembrane potentials and automaticity in the dog.

Previous studies have shown that alpha adrenergic stimulation can reduce the automaticity of canine Purkinje fibers. In the present study, our interest was to determine whether this is an alpha-1 or alpha-2 adrenergic action. We used standard microelectrode techniques to study the effects of the alpha agonists, phenylephrine and clonidine, and the alpha antagonists, prazosin and yohimbine, on phenylephrine-induced decreases in automaticity. Prazosin and yohimbine, 1 X 10(-5) M, alone, significantly reduced the amplitude and upstroke velocity (Vmax) of stimulated action potentials. In addition, yohimbine, 1 X 10(-5) M, accelerated and prazosin, 1 X 10(-5) M, attenuated repolarization. Prazosin, 1 X 10(-5) M, and yohimbine greater than or equal to 1 X 10(-7) M, alone, decreased automaticity. Phenylephrine, 5 X 10(-8) M, alone, significantly increased the cycle length of automatic Purkinje fibers. The effects of phenylephrine on automaticity were blocked by prazosin but not by yohimbine. Clonidine, alone, 1 X 10(-6) and 1 X 10(-5) M, significantly reduced automaticity, an effect that was not blocked by yohimbine or prazosin. Clonidine, 1 X 10(-6) and 1 X 10(-5) M, also significantly reduced Vmax and prolonged action potential duration of driven Purkinje fibers, an action consistent with direct membrane effects. These experiments suggest that the negative chronotropic effects of phenylephrine on Purkinje fiber automaticity are mediated by alpha-1 adrenergic receptors.

Adrenergic alpha-Agonists↗

PubMed1984

Developmental changes in action potential duration, refractoriness, and conduction in the canine ventricular conducting system.

The purpose of these studies was to determine the age-related changes that occur in refractoriness and conduction in the canine Purkinje system and ventricle. We used standard microelectrode techniques to study the isolated left and right ventricular specialized conducting system of neonatal and 2-, 5-, and 10-year-old beagles. We mapped the preparations with microelectrodes and bipolar surface electrodes and recorded action potential duration, conduction velocity, and refractoriness. We found five age-related changes. (1) The region of maximum action potential duration in the adult Purkinje system occurred in the distal false tendon near its subendocardial insertion. In neonates, the entire proximal subendocardial Purkinje system and free running false tendon had a uniformly long action potential, which then shortened in the distal subendocardial fibers. (2) Conduction block of responses to induced premature stimuli occurred proximally, near the origin of the false tendon in all groups. (3) The effective refractory period of the ventricular specialized conduction system did not vary among different age groups and was the same for the left and right ventricles. (4) Conduction velocity of basic and premature impulses was significantly lower in neonates and higher in 2-year-olds than in older age groups; (5) values for amplitude and maximum upstroke velocity of phase 0 were reduced in the neonatal and 10-year-old beagles with respect to values for 2- and 5-year-old beagles.

Action Potentials↗

PubMed1983

An electrophysiologic study of the digoxin--quinidine interaction.

To study the electrophysiologic mechanisms responsible for the digitalis-quinidine interaction, 27 mongrel dogs were given either quinidine alone, digoxin alone, or digoxin followed by the digoxin-quinidine combination, via the oral route for sufficient time to permit accumulation of steady-state plasma levels. As anticipated, digoxin levels increased significantly in the presence of quinidine (P less than 0.05). Whereas digoxin alone had no significant effect on the ECG, quinidine alone prolonged the Q-T interval (P less than 0.05), and the combination prolonged both the QRS complex and the Q-T interval (P less than 0.05). Digoxin alone had no significant effect on the Purkinje fiber transmembrane potential, whereas quinidine reduced action potential (AP) amplitude and maximum upstroke velocity (Vmax) significantly. The combination significantly reduced AP amplitude Vmax, and maximum diastolic potential and prolonged AP reduced AP amplitude, Vmax, and maximum diastolic potential and prolonged AP duration. The changes induced by the drug combination appeared to be the sum of changes induced by each drug alone.

Animals↗

PubMed1983

Actions of adenosine on normal and abnormal impulse initiation in canine ventricle.

We studied the role of adenosine in modulating pacemaker activity in normal and infarcted ventricular tissues. We used standard microelectrode techniques to study the effects of adenosine on impulse initiation in Tyrode's superfused normal canine Purkinje fibers (PF), PF obtained from experimentally infarcted hearts, and BaCl2-superfused PF. Adenosine reduced automaticity of normal PF, whereas beta, gamma-methylene ATP did not. In infarcted and in Ba2+-depolarized PF, adenosine had no effect on automaticity or the action potential. We then used intracellular current injection to vary the membrane potentials of normal PF and found adenosine to depress automaticity more at high than at low membrane potentials. The ability of adenosine to counteract the effects of epinephrine on automaticity also was related to membrane potential. We conclude that adenosine depresses normal automaticity but has little effect on abnormal impulse initiation at low membrane potentials. It therefore appears that in the setting of myocardial infarction or ischemia the extent to which adenosine release will modify the function of normal and ectopic pacemakers will be influenced by the membrane potentials of those pacemakers.

Adenosine↗

PubMed1983

Isolated myocytes from adult canine left ventricle: Ca2+ tolerance, electrophysiology, and ultrastructure.

We have developed a method for isolating single cardiac muscle cells in high yield (greater than 5 X 10(7) cells) from the canine left ventricle. Most of the myocytes are single cells with ultrastructural detail indistinguishable from intact ventricular myocardium, and more than 50% of the isolated cells remain elongated for at least 7 h in 0.5 mM calcium. Electrophysiological studies demonstrate that external potassium has a strong influence on repolarization in the isolated ventricular cells. Action potentials in [K+]o = 3.78 mM exhibit a positive over-shoot (greater than zero potential), but repolarization often arrests at congruent to -35 mV unless driven to more negative potentials by hyperpolarizing current. This phenomenon of two levels of resting potential is not observed at [K+]o = 5.78 mM. At the higher potassium concentration, values for maximum diastolic potential, amplitude, maximum rate of rise of phase 0, and action potential duration all are similar to those of intact ventricular muscle. However, the potential at the peak of the action potential plateau (phase 2) in the isolated myocyte is considerably more negative than that of intact myocardium. In addition, there is a conspicuous notch between phases 1 and 2 of the action potential in the isolated myocyte, whereas the notch is small or absent in intact myocardial action potentials. In summary, our method results in a preparation of stable, ultrastructurally and electrophysiologically intact cells, which should prove useful in studies requiring a large and homogeneous population of myocardial cells.

Action Potentials↗

PubMed1983

Developmental changes in the cardiac effects of amrinone in the dog.

Amrinone, a bipyridine compound, has been shown to exert a positive inotropic effect on the heart, without producing cardiac arrhythmias. Because of preliminary observations suggesting that the actions of amrinone might change significantly with growth and development, we studied its effects on the contractility and electrophysiology of isolated cardiac muscle of 0- to 96-day-old beagles and Purkinje fibers of 5-year-old beagles. Amrinone's effects on ventricular muscle contractility were age-related. A significant decrease in contractility of right ventricular trabeculae and papillary muscles (not associated with changes in action potential characteristics) was observed in the 0- to 3-day newborn, whereas, by day 4-10, amrinone increased contractility. The magnitude of the increase became greater through day 96 of life. The negative inotropic effect of amrinone is unassociated with changes in the action potential plateau, suggesting that the slow inward current is not involved in this mechanism.

Aging↗

PubMed1982

Fast and slow idioventricular rhythms in the canine heart: a study of their mechanism using antiarrhythmic drugs and electrophysiologic testing.

Complete heart block in dogs was induced by injecting the His bundle with formalin. For the 1st few days after surgery, a fast idioventricular rhythm (cycle length 471 +/- 37 ms, mean +/- standard error of the mean) occurred either as the only ventricular rhythm or interspersed with a slow idioventricular rhythm (cycle length 1,307 +/- 17 ms). The response to cardiac pacing, lidocaine, ethmozin and verapamil in conscious dogs was studied 1 day and 1 to 2 weeks after surgery. The fast idioventricular rhythm could not be suppressed by overdrive pacing, and at times its rate actually increased after pacing. The basic length of the fast idioventricular rhythm was prolonged by ethmozin but not by verapamil or lidocaine. The recovery cycle length ( that is, that of the first beat after cessation of overdrive pacing) was prolonged by ethmozin and verapamil, but not lidocaine. The slow rhythm was suppressed by overdrive pacing and its rate was decreased by lidocaine, unaltered by ethmozin and increased by verapamil. The recovery cycle length of the slow rhythm also was prolonged by lidocaine, unaltered by ethmozin and decreased by verapamil. The results are consistent with the slow rhythm resulting from normal automaticity (that is, that which occurs at high levels of membrane potential and is overdrive-suppressed) and the fast rhythm resulting from an abnormal automatic mechanism (that which occurs at low membrane potentials and is not overdrive-suppressed). The results obtained with verapamil are consistent with drug-induced catecholamine release.

Animals↗

PubMed1982

alpha- and beta-Adrenergic effects of epinephrine on ventricular pacemakers in dogs.

We studied the effects of epinephrine on idioventricular rhythm in 15 adult dogs with chronic complete heart block induced by the injection of formalin into the His bundle. Atropine (0.1 mg/kg) was given intravenously to attenuate any potential vagal effects, and epinephrine was infused in graded doses of 0.01-10.0 micrograms.kg-1.min-1. Two different responses were seen. In 12 dogs there was a concentration-dependent increase in ventricular rate following epinephrine infusion. These animals then were given the beta-blocker propranolol (0.5 mg/kg iv), and the epinephrine infusions were repeated. In this situation epinephrine concentrations less than 0.1 micrograms.kg-1.min-1 induced a decrease in ventricular rate with no associated change in arterial pressure. In four additional dogs this decrease in ventricular rate was prevented by alpha-blockade with phentolamine. In three dogs epinephrine less than 0.1 micrograms.kg-1.min-1 induced a decrease in ventricular rate without an associated change in arterial blood pressure. This decrease in rate was abolished by the alpha-blocker phentolamine. It therefore appears that an alpha-adrenergic effect on ventricular automaticity can occur in the intact animals. When this does not occur initially, it can be unmasked by propranolol and results in a slowing of ventricular rate unrelated to changes in blood pressure.

Animals↗